Ca2+ signalling in heart displays a complex and dynamic sensitivity to pH. H+ ions are end products of metabolism and must be removed if cellular function is to be maintained. Despite this, local reversible changes of extracellular and intracellular pH (pHo & pHi) are common occurrences, for example, during an increase in myocardial workload or a decrease in vascular perfusion, an extreme example being myocardial ischaemia. The talk will focus on three nodes within the Ca2+ signalling pathway of the ventricular myocyte, where pH is sensed and then transduced into a modified signalling code. (i) The dihydropyridine receptor (Cav1.2 protein) responsible for the L-type Ca2+ current (ICaL) displays a steep differential sensitivity to pHo where a fall is inhibitory, and to pHi, where a fall is excitatory. These effects can be additive and are often overlaid by an additional secondary influence on the Cav1.2 channel caused by pH-induced changes of diastolic Ca2+. (ii) Sarcolemmal Na+ /H+ exchange (NHE) and Na+ -HCO3- cotransport (NBC) sense a fall of pH and export acid from the cell, while importing Na+ ions. The resulting rise of Na+, by acting on sarcolemmal/t-system Na+/Ca2+ exchange (NCX), raises Ca2+, ultimately in the lumen of the sarcoplasmic reticulum, but far less noticeably within bulk cytoplasm. The SR load results in an increased Ca2+ -release during an action potential, thus increasing the Ca2+ transient (CaT), and hence contraction. (iii) Diastolic cytoplasmic Ca2+ is, surprisingly insensitive to the elevation of Na+i induced by NHE/NBC during acidosis. There is an acid-induced rise of diastolic Ca2+, but this is independent of NHE/NBC activity. It is caused by Ca2+ release from local sources within the myocyte. The resulting elevation of Ca2+ maps fairly precisely onto any local, spatial variation of cytoplasmic pH. The mechanism that induces these pH-dependent Ca2+ microdomains is an active process, relying on the magnitude of the local H+i-non-uniformity and upon ambient levels of ATP generated by mitochondrial and glycolytic metabolism. The possible mechanism involved will be explored in the lecture. The integrated `response of the myocyte to the pH-sensing and transduction system will be demonstrated by coding the system’s parameters into computational models of ventricular myocyte Ca signalling and the action potential. One insight is that intracellular acidosis induces intracellular Ca2+ loading via multiple pathways while extracellular acidosis reduces this. The H+ ion emerges as a major controller of intracellular Ca2+ dynamics in the myocardium.